The object of this proposal is to understand the principles involved in the metabolic regulation of normal and sickle-cell erythrocytes. Particular emphasis will be placed on the study of those enzymes responsible for 2,3 diphosphoglycerate synthesis and utilization. The enzymes currently under investigation include: diphosphoglycerate mutase and monophoglycerate mutase. Each of these enzymes will be isolated to homogeneity and will be characterized both catalytically and physicochemically. This study will also include an evaluation of certain intracellular environmental conditions and potentially regulatory substances which might prove beneficial in the treatment of sickle-cell disease and, perhaps, other pathological cardiovascular conditions.